Efficacy of histology-agnostic and molecularly-driven HER2 inhibitors for refractory cancers

Luc Cabel, Alina Fuerea, Ludovic Lacroix, Capucine Baldini, Patricia Martin, Antoine Hollebecque, Sophie Postel-Vinay, Andrea Varga, Rastilav Balheda, Anas Gazzah, Jean Marie Michot, Aurélien Marabelle, Etienne Rouleau, Eric Solary, Thierry D. De Baere, Eric Angevin, Jean Pierre Armand, Stefan Michiels, Jean Yves Scoazec, Samy AmmariFabrice André, Jean Charles Soria, Christophe Massard, Loic Verlingue

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    13 Citations (Scopus)

    Résumé

    A targeted therapy is recommended in case of ERBB2 alteration for breast and gastric carcinomas, but miscellaneous other tumor types are ERBB2-altered at low prevalence. Broadening the administration of HER2 inhibitors across tumor types and genomic alterations could benefit to patients with refractory metastatic tumors. Targeted next-generation-sequencing (tNGS) and comparative genomic hybridization array (CGH) have been performed on fresh tumor biopsies of patients included in the MOSCATO-01 and ongoing MOSCATO-02 trials to administrate HER2 inhibitors in case of ERBB2 pathogenic mutation of amplification. Between December 2011 and January 2017 a molecular analysis was performed for 934 patients (759 CGH and 912 tNGS). A novel ERBB2 alteration has been found in 4.7% (n = 44/934), including 1.5% (n = 14/912) ERBB2 mutations, and 4% (n = 30/759) ERBB2 amplifications. A matched HER2 inhibitor was administrated to 70% (31/44) of patients and consisted in trastuzumab plus chemotherapy for 90% of them (28/31). On the 31 evaluable patients, 1 complete response (CR), 10 partial response (PR) and 2 stable disease (SD) > 24 weeks were observed accounting for a clinical benefit rate (CBR) of 42% (n = 13/31, 95% CI 25-61%). Besides breast and oesogastric carcinomas, 19 patients affected by 8 different tumor types had a CBR of 25% for ERBB2 mutations (n = 2/8, 95% CI 3%-65%, with 2 PR) and 64% for ERBB2 amplifications (n = 7/11, 95% CI 31%-89%; with 1 CR, 4 PR, 2 SD).

    langue originaleAnglais
    Pages (de - à)9741-9750
    Nombre de pages10
    journalOncotarget
    Volume9
    Numéro de publication11
    Les DOIs
    étatPublié - 1 janv. 2018

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